tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes among males undergoing prostate cancer germline testing: Interim results from the Prostate Cancer Genetic Risk, Experience, and Support Study (PROGRESS) Registry.
Authors: Veda N. Giri, Rebecca L. Hartman, Laura Gross, Scott W. Keith
Journal: Journal of Clinical Oncology (2022)

10595 Background: Indications for prostate cancer (PCA) germline testing (GT) have greatly expanded, necessitating thousands of men to seek genetic evaluation through traditional genetic counseling and alternate delivery approaches. Therefore, there is an important need for patient-reported outcomes among men undergoing genetic testing which has been understudied. PROGRESS (Prostate Cancer Genetic Risk, Experience, and Support Study) was therefore developed to garner men’s experience with PCA germline testing. Here we provide an interim update on recruitment and results from registry participants. Methods: PROGRESS is a patient-driven registry of clinical, genetic, and patient-experience information among men undergoing PCA genetic testing. Survey covers demographic information, PCA history, mode of genetic counseling, satisfaction, decisional conflict, intention to share genetic results with family and physicians, attitude towards genetic testing, knowledge of cancer genetics, medical literacy, and numeracy. Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. All analyses were performed with SAS 9.4 (Cary, NC). Results: Current enrollment is 217 participants. Among 140 men with complete demographics, 93.57% are White, 98.6% non-Hispanic/Latino, 85% with bachelor’s degree or higher. Among 143 respondents, 60% reported a diagnosis of PCA. Among 85 men who reported on Gleason score, 24.7% had Gleason &gt; = 8. Regarding family history, 23.5% reported a 1 st /2 nd degree relative with PCA and 58.1% reported a 1 st /2 nd degree relative with any cancer. Among 150 men who reported genetic results, 40.7% had a genetic mutation, 18% reported having a VUS, and 10.7% reported not knowing their results. Among 185 men who reported on mode of genetic evaluation, 58.4% met with a genetics professional and 21.7% reported their doctor had discussed genetic testing. Satisfaction was high (n = 121) (highest score 30; mean score 27.92 + 2.73) and decisional conflict was low (n = 138) (mean score 26.07 + 10.18; range 16-80). Majority of 140 respondents discussed their results with their family (93.6%). Knowledge of cancer genetics was modest, with correct responses among 140 respondents of 50.1% + 28.1. Conclusions: Current participants of the PROGRESS Registry report high satisfaction with their genetic evaluation process. However, resources are needed to increase knowledge and understanding of genetic results. Greater engagement of African American males is critically needed to garner diverse perspectives and develop resources for men and their families applicable across populations. Target goal of the registry is 500 males; men can be referred to participate in the PROGRESS Registry at www.progressregistry.com .
Canadian oncology residents’ knowledge of and attitudes towards artificial intelligence and machine learning.
Authors: Thomas Kennedy, Laura Collie, Jacqueline J. Nabhen, Fabio Ynoe de Moraes
Journal: Journal of Clinical Oncology (2022)

e13587 Background: The use of artificial intelligence (AI) and machine learning is becoming more common and is expected to expand further in order to meet the needs of our ever-evolving healthcare system. In oncology, AI and machine learning are already being explored in various applications. Despite AI’s importance, there is sparse formal teaching on AI incorporated into medical schools’ curricula and residency training programs. In this study, we examined the perceptions and knowledge of Canadian oncology residents and fellows with respect to AI technologies. Methods: An electronic, anonymous, questionnaire-based survey was distributed to residents and fellows in medical and radiation oncology programs across Canada. Survey questions spanned areas of demographics, familiarity with AI, personal attitudes towards AI, and perspectives regarding AI use in different specialties. Approval was obtained from the Queen’s Research Ethics Board prior to conducting this study. Mixed-methods statistical analysis is ongoing. Qualitative data will be analyzed using thematic analysis. Univariable and multivariable regressions will be conducted to identify any correlation between perception or knowledge of AI and demographic factors. Results: Fifty-seven participants responded in total. Most residents (67%) agreed or strongly agreed that it was important they learn about AI. Seventy percent indicated that, if given the chance, they would like to learn more about AI, yet the majority of participants (88%) indicated they had not received formalized teaching. Disciplines that were felt to be most associated with AI were radiology (98%), radiation oncology (84%), and pathology (58%). With respect to the field of radiation oncology, 98% of respondents felt that AI had the potential to replace some, most, or all medical activities. A perceived barrier to understanding AI was a lack of knowledge of mathematics and programming (63%). Respondents indicated that their preferred formats for learning about AI would be workshops (78%), lectures (60%), and collaborative activities with other departments (46%). Conclusions: Our results show that Canadian oncology residents’ sense that AI is important and relevant to their area of training. Despite this, they have not received education on these topics. Thus, formalized teaching, such as lectures and workshops, would be perceived as beneficial by most Canadian oncology residents.
Variation in recurrence rate and overall survival (OS) outcomes by disease stage and incremental impact of time to recurrence on OS in localized renal cell carcinoma (RCC).
Authors: Naomi B. Haas, Rituparna Bhattacharya, Yan Song, Jackie Rogerio, Su Zhang, Christopher Carley, Annika Anderson, James Signorovitch, Murali Sundaram
Journal: Journal of Clinical Oncology (2022)

4543 Background: Prior research shows that post-nephrectomy recurrence is correlated with significantly increased mortality in patients (pts) with intermediate-high (int-high) risk and high risk RCC. However, no study has quantified the incremental OS associated with increased time to recurrence (ToR). Additionally, limited evidence is presented on the variation of recurrence rate and OS by stage of RCC. Methods: The SEER-Medicare database (2007–2016) was used in this retrospective observational study. Post-nephrectomy pts with newly diagnosed, int-high risk (pT2 N0 high grade, pT3 N0 any grade) or high-risk (pT4 N0 any grade, pT any N1 any grade) RCC were identified and stratified based on tumor stage and grade. Grade was defined based on Furhman grading system and was reported in SEER Registry. Post-nephrectomy recurrence free rates and OS by disease stage were described using Kaplan-Meier analyses. OS from nephrectomy in pts with recurrence vs pts without recurrence was compared by disease stage. Multivariable regression analysis was used to quantify the incremental OS associated with increased ToR post-nephrectomy in all pts with recurrence. Results: 643 pts met the inclusion criteria (269 with vs 374 without recurrence; median follow-up: 23 months). The mean age was 75.5 years (yrs), 61% male, and 86% white. Results presented in the table showed wide variance in 5-yr recurrence-free rate in int-high risk group (28%-63%) and indicated substantial risk of disease recurrence in all subgroups of int-high risk pts. Among those with T3 Grade 1-2, T3 Grade 3, and T3 Grade 4 disease, pts with recurrence had significantly higher risk of death than those without (all ps&lt;0.05;). Results for pts with T2 and T4 disease were not presented due to small sample size. Multivariable regression analysis indicated that 1 additional yr of ToR was associated with 0.73 additional yrs (8.8 additional months) of OS post nephrectomy (95% CI: 0.40, 1.05 yrs; p&lt;0.001). Conclusions: The non-trivial recurrence rates observed in pts with T3 Grade 1-2 and T3 Grade 3 RCC highlighted the substantial risk of recurrence and unmet needs in the int-high risk RCC patients. This study also confirms the incremental nature of the association of ToR and OS in patients with int-high and high risk localized RCC. These findings highlight the need for effective early intervention with adjuvant treatments in int-high and high risk post-nephrectomy RCC pts. [Table: see text]
Second primary malignancies (SPM) in patients with gastrointestinal stromal tumors (GIST): 10-year experience from the Ottawa Hospital (TOH).
Authors: Abdulhameed Alfagih, Bader Alshamsan, Abdulaziz AlJassim, Nasser Alqahtani, Timothy R. Asmis
Journal: Journal of Clinical Oncology (2022)

11536 Background: The secondary malignancies in patients with GIST are relatively high. We present our 10-year experience of SPM in patients with GIST from a regional Cancer Centre in Canada. Methods: A retrospective cohort study was performed in all GIST patients treated at TOH between January 2011 and December 2021. Patients were identified using ICD-10 codes and electronic medical records reviewed. Clinicopathological data were analyzed. Logistic regression analysis was used to evaluate associated factors with SPM. Survival analysis was estimated with the use of the Kaplan-Meir method and compared by log-rank test. Results: In total, 248 patients with GIST were identified. Of these patients, 61 (25%) had SPM; synchronous (9, 15%) and metachronous (52, 85%). Nine patients had two additional primary cancers other than GIST, and four patients had three additional primary cancers. The median age at diagnosis was 70 (range 44 – 90) years, and males were (59%). The most common SPMs were skin cancer (14, 17%), melanoma (5), and non-melanoma (9), followed by prostate cancer (13, 16%) and breast cancer (12, 15%). Colorectal cancer and hematological malignancies were found in (5, 11%) patients each, while RCC was found in (4, 6%). Thyroid cancer, lung cancer, neuroendocrine tumor, bladder cancer, thymoma, and other types of cancers were collectively found in 15 patients (24%). The majority (57%) of SPM diagnosed before GIST, 30% after GIST. The most common primary GIST locations were in the stomach (62%), followed by the small bowel (30%), and the most common histology was spindle cell (69%), followed by mixed histology (13%). The majority of GIST were localized (46 patients, 75%). Based on Miettinen risk classes for non-metastatic GIST, 74% had zero to low-risk disease, while 26% had moderate or high-risk disease. There was no association between SPM and GIST primary site (p = 0.4), TNM stage (p = 0.8), histology (p = 0.2), Mitosis (p = 0.5), and Miettinen risk class (p = 0.6). The median follow-up time was 53 months (range 1 – 132), and four patients lost follow-ups. Five years overall survival of SPM group vs. non SPM, 79.8% vs. 94.1%, (p = 0.03). Cox regression did not reveal a significant association with the covariants Conclusions: We observed that one out of four GIST patients have SPM. Skin, prostate, breast cancers were the most common SPM associated with GIST. Molecular studies are needed to explore the association/underlying mechanisms of GIST with these malignancies.
Feasibility of a novel wrist-worn thermal device for management of vasomotor symptoms in patients with prostate cancer.
Authors: Alicia K. Morgans, Sonja K Billes, Andrew Vetter, Nader Naghavi, Diana Le, Matthew Smith, Pamela Peeke
Journal: Journal of Clinical Oncology (2022)

5067 Background: Vasomotor symptoms (VMS), or hot flashes, are a common side effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). VMS negatively impact sleep, fatigue, and quality of life (QOL) in PCa survivors. There are few nonpharmacological treatments for VMS. The Embr Wave is a wearable thermal device that applies cooling to thermoreceptors on the inside of the wrist and has been associated with patient reported decreases in hot flash interference in women. We performed a single-arm feasibility study evaluating the Embr Wave for management of VMS in PCa survivors. Methods: 57 PCa survivors reporting bothersome hot flashes were enrolled and instructed to use the device as needed for VMS during the 4-week study. The primary outcome was device usage recorded by the device (minutes and sessions). Additional outcomes included the change in patient reported Hot Flash Related Daily Interference Scale (HFRDIS, range 0-10) and Patient Reported Outcomes Measurement Information System Sleep Disturbance 4a (PROMIS SD, range 0-100) and Sleep Related Impairment 8a (PROMIS SRI, range 0-100). Study procedures were conducted remotely using a virtual clinical trial management platform. Results: The study was conducted from May to Dec 2021 in the US. 44 men completed the study; 39 had retrievable usage data. Median age was 66 (range 57-78) years and median 3 (1-23) years since PCa diagnosis. The most common hormonal treatments were leuprolide (n=22), abiraterone (n=13), and enzalutamide (n=6). Baseline scores indicated moderate hot flash interference and mild sleep disturbance (Table). Mean±SD (median) usage of the Embr device was 3.2±2.5 (2.3) hours and 7.6±3.6 (7.5) sessions per day. 26 (67%) participants reported using the device 7 days/nights each week. Improvements were observed in HFRDIS, PROMIS SD, and PROMIS SRI scores (Table). There were also improvements in subjective ratings of hot flash frequency, duration, interference with daily life/sleep, bothersomeness and control (all p&lt;0.01). The majority (69%) of participants reported that the device was effective at helping them manage hot flashes. No adverse events were reported. Conclusions: Results of this study support the feasibility of use of the thermal device for management of bothersome hot flashes in PCa survivors. Future randomized controlled studies are warranted to evaluate patient reported outcomes related to frequency and severity of VMS, sleep quality, fatigue, and overall QOL, in addition to defining the potential utility of the Embr thermal device in PCa survivors experiencing VMS. Clinical trial information: NCT04892914. [Table: see text]
Advanced care planning (ACP) intervention for older patient with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
Authors: Marissa LoCastro, Chandrika Sanapala, Erin Watson, Benzi Kluger, Sally Norton, Rachelle Bernacki, Thomas Carroll, Heidi D. Klepin, Jason Mendler, Kah Poh Loh
Journal: Journal of Clinical Oncology (2022)

e19004 Background: The Serious Illness Care Program (SICP) is an evidence-based intervention that promotes ACP for patients with advanced cancer. As part of a study to adapt the SICP for older patients with AML and MDS, we identified clinician and patient reported barriers to ACP for this population, and their suggestions to improve ACP. Methods: In single-center qualitative study, we conducted semi-structured interviews with 14 oncology clinicians and 7 patients with AML or MDS. Interviews were audio-recorded and transcribed. Two investigators independently coded all transcripts using MAXQDA and resolved discrepancies through iteration. Direct content analysis techniques were used to focus on ACP barriers and suggestions. Results: Mean ages of clinicians and patients were 45 and 73, respectively. Majority of patients were not familiar with ACP. All patients had a healthcare proxy. Half of patients were familiar with a Medical Orders for Life-Sustaining Treatment (MOLST) form. Two major themes identified by clinicians and patients were: 1) Discomfort and logistics as ACP barriers (Table) and 2) ACP visit structure. Both clinicians and patients suggested the importance of earlier ACP visits. Clinicians suggested separate outpatient ACP visits, while patients suggested ACP after in-depth treatment discussion. Conclusions: Discomfort and logistics were identified as major barriers to ACP. Initiating ACP earlier was identified as a possible solution by clinicians and patients. Feedback obtained will be used to adapt the SICP to be delivered via Telehealth in a single arm pilot study.[Table: see text]
A deep learning approach to discover cyclin-dependent kinases 12 (CDK12) inhibitors in breast cancer.
Authors: Tingyu Wen, Lixi Li, Yiqun Li, Jun Wang, Peng Gao, Guotong Xie, Fei Ma
Journal: Journal of Clinical Oncology (2022)

e15086 Background: Although anti-HER2 tyrosine kinase inhibitors (TKIs) have significantly prolonged survival and improved prognosis in HER2-positive breast cancer patients, resistance is a constant obstacle leading to TKIs treatment failure and tumor progression. Our previous research shows dual inhibition of HER2/CDK12 will prominently benefit the outcomes of patients with HER2-positive breast cancer by sensitizing the tumors to anti-HER2 TKIs treatment. Unfortunately, there is no high selective CDK12 inhibitor in clinical. This study sought to accelerate the CDK12 inhibitor discovery by a deep learning approach. Methods: We developed a large-scale self-supervised graph neural network to learn 11 million unlabelled compounds for molecular representation. And the model was trained with 233,823 kinase domain sequences by drug-target interaction datasets from the BindingDB database. Then, this transformer architecture was used to predict potential CDK12 inhibitors. The candidate hits compounds with diverse skeletons were divided into 50 clusters by clustering analysis. The representative hits with high transform scores and rational binding mode in each cluster were detected in the homogeneous time-resolved fluorescence CDK12 kinase assay. Candidate clusters with half-maximal inhibitory concentrations (IC50) lower than 200 nM were selected into expanded validation and kinase selective panel detection. xCELLigence RTCA system was adopted to monitor cell growth and sensitivity of breast cancer cells to CDK12 inhibitors in a real-time manner. Results: Our predictive transfer learning model yielded satisfactory predictions on various targets including CDK12. We screened a total of 4,527,236 compounds and recommended 50 clusters of potential CDK12 inhibitors for further enzyme activity detection. The IC50 of seven cluster representative compounds is lower than 10 uM. Expanded screening of 500 compounds in these clusters discovered a lot of hits with highly CDK12 selective inhibition. Half of the new compounds are showed promising proliferation inhibition in breast cancer cell lines. Conclusions: Our study provides a highly efficient and end-to-end deep learning approach to discover highly selective CDK12 inhibitors in breast cancer.
Recurrence, metastasis, and survival after radical prostatectomy in the era of advanced treatments.
Authors: Kristian D. Stensland, Megan Veresh Caram, Jennifer A. Burns, Jordan B. Sparks, Chris Shin, Alexander Zaslavsky, Brent K. Hollenbeck, Alexander Tsodikov, Ted A. Skolarus
Journal: Journal of Clinical Oncology (2022)

5090 Background: Accurate survival estimates after prostatectomy are critical for patient counseling, treatment decisions, and trial design. Prior prostate cancer natural history studies may not reflect contemporary outcomes and often lack key endpoints (e.g. incident metastases). For these reasons, we explored population-based recurrence and survival following radical prostatectomy. Methods: We conducted a retrospective study of men with localized prostate cancer treated with radical prostatectomy from 2005-2015 with follow up through 2019 in the Veterans Health Administration. We excluded men with adjuvant radiation or hormonal therapy and defined biochemical recurrence (BCR) as a PSA ≥0.2 ng/mL. We used a validated natural language processing encoded dataset to identify incident metastatic disease. We then estimated actuarial time from surgery to BCR, BCR to metastatic disease, and metastatic disease to death using Kaplan-Meier methods. Results: Of 22,033 men post-prostatectomy, 5,963 (27%) developed BCR, with 5- and 10-year BCR estimates of 21% and 29% (Table). Of 5,963 men with BCR, 678 (11%) developed metastasis, with 5- and 10-year metastasis-free survival from time of BCR of 91% and 77%. Of these 678 men with metastases, 235 died (35%), with 5- and 10-year overall survival of 61% and 47%. Median actuarial overall survival from incident metastatic disease was 8.8 years. Conclusions: On average, we found a man undergoing radical prostatectomy for localized prostate cancer can expect about a 1 in 4 chance of biochemical recurrence. Of men with BCR, we identified a 1 in 10 chance of developing metastases, surviving nearly 9 years after incident metastasis. Both metastasis-free survival after biochemical recurrence and overall survival after developing metastasis appear to have lengthened consistent with a long natural history after prostate cancer surgery. Novel advanced prostate cancer treatments may help explain these findings, though their optimal use warrants further study especially as advanced imaging techniques to characterize recurrence increase. [Table: see text]
Survival among patients with multiple myeloma in the U.S. military health system compared to the Surveillance, Epidemiology, and End Results (SEER) program.
Authors: Alexander Dew, Sarah Darmon, Jie Lin, Jason Ware, Joseph Lee Roswarski, Craig D Shriver, Kangmin Zhu, Alden Vincent Chiu
Journal: Journal of Clinical Oncology (2022)

6524 Background: Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite therapeutic advances. The US Military Health System (MHS) provides universal healthcare to beneficiaries and has been associated with improved survival across multiple malignancies. It is unknown whether access to universal healthcare via the MHS translates to improved survival for MM patients. We sought to answer this question by comparing survival data from the Department of Defense’s Automated Central Tumor Registry (ACTUR) and the NCI’s SEER database. Methods: Patients 18 years and older diagnosed with histologically confirmed MM between 1987-2013 were identified in ACTUR (N=1,488) and SEER (N=2,976) databases. Two SEER patients were matched to an ACTUR patient by age group, sex, race, and diagnosis year group. Five and 10-year survival was compared between ACTUR and SEER patients using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) adjusted for potential confounders of age at diagnosis, sex, race and diagnosis year. The proportional hazards assumption for the analysis was assessed with log-log survival curves. Results: Median survival in the ACTUR patients was 47.1 months (95% CI: 43.9-50.4) compared to 33.0 months (95% CI: 32.0-35.0) in the SEER group. Five and 10-year survival was superior in patients from the ACTUR group compared to the SEER group with an aHR of 0.74 (95% CI: 0.68-0.81) and 0.79 (95% CI: 0.74-0.85) after adjustment for potential confounders, respectively. The survival advantage of ACTUR patients was preserved when stratified by age, sex, race, and diagnosis year. Conclusions: Patients treated with MM in the MHS had superior 5 and 10-year overall survival when compared to the general population. This benefit remained despite age, sex, race, and diagnosis year. Our study findings suggest the benefits of universal healthcare provided by the MHS improve survival among MM patients. Further research is warranted to delineate factors which improve survival and reduce disparity in the treatment of MM patients.[Table: see text]